All ETDs from UAB

Advisory Committee Chair

Lori L McMahon

Advisory Committee Members

Lynn Dobrunz

Document Type

Thesis

Date of Award

2014

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Learning is the process in which new information is acquired and requires cellular modifications that occur in the hippocampus. These cellular changes can be seen through behavioral modifications which indicate memorization of the previously learned material. Increases in phosphorylation of the extracellular regulated protein kinase (ERK), a subfamily of MAPKs alters synaptic efficacy making it a correlate for learning and memory. Additionally, surges in plasma 17ß estradiol (E2) levels can increase synaptic plasticity, suggesting an importance for the role of E2 in cognition. Both human and animals studies have shown that elevated levels of estrogen correlated to an enhancement in learning and memory associated tasks. Moreover during menopause, a state of estrogen deprivation, women have reported decreases in executive functioning. In addition to decreased cognition, studies have shown that plasma levels of the neuropeptide orexins (hypocretins) are increased in menopausal women when compared to that of non-menopausal women. Our lab has shown a tight correlation of the estrogen-induced enhancement in memory to be highly dependent upon increases in GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) because this enhancement is prevented when GluN2Bs are pharmacologically blocked in the hippocampus in vivo. The goal of this study was to first test the hypothesis that the mechanisms downstream of GluN2Bs, ERK, will be increased by E2 administration in our animal model of menopause because E2 has the ability to increase transmission through NMDARs. This will show that the two mechanisms are synchronously coupled to facilitate plasticity changes in the hippocampus. Additionally, this thesis proposed that in the presence of circulating estrogen, orexin levels will be lower than those of animals who did not receive E2 treatment suggesting that E2 has the ability to regulate orexin levels in the brain. This thesis shows that E2 increases pERK levels and these increases are region specific and may not be due to transmission through NMDARs. It also shows that in our animal model of menopause, there is no difference in orexin levels with E2 treatment.

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